5-Fluorouracil (5FU) is a component of several combination chemotherapy protocols. Little is kn wn about the effects of other drugs upon its disposition. Neither is there much information concerning the effects of 5-FU on the hepatic microsomal enzymes. This study is designed to identify factors which regulate 5-FU catabolism. Isolated perfused rat livers, hepatocytes in suspension and breath tests in intact animals will be used to assess 5-FU metabolism after a variety of experimental maneuvers. Hepatic drug metabolism will be evaluated in microsomes and by using an aminopyrine breath test. Particular emphasis will be placed on elucidating the effects of various dosage schedules and combinations of chemotherapeutic agents on the metabolism of 5-FU and on microsomal enzyme activity. Potential drug-drug interactions will be studied. In addition, nutritional influences on 5-FU catabolism will be investigated.